Comparison of Experimental Lung Injury from Acute Renal Failure with Injury due to Sepsis

Abstract

Background: Acute renal failure (ARF) and acute respiratory distress syndrome (ARDS) coexist frequently, and the mortality rate of this combination is very high. It is well established that cytokines and chemokines play a major role in the pathogenesis of ARDS. In addition, heat shock proteins (HSPs) have been shown to be protective against ARDS. Objectives: The purpose of this study was to investigate the pathophysiology of ARDS in two different conditions, sepsis and ARF. Methods: We examined five different rat animal models including sham-operated control, sepsis and three ARF models induced by renal ischemia/reperfusion injury, bilateral nephrectomy or bilateral ligation of renal pedicles. We analyzed pulmonary histology, pulmonary vascular permeability, cellular infiltration, and expression of cytokines, chemokines and HSPs. Results: Like sepsis, the three forms of ARF led to ARDS, as manifested by increased pulmonary vascular permeability and histological changes consistent with ARDS. On the other hand, ARF and sepsis differed in that ARF was associated with markedly lower levels of pulmonary cellular infiltration. Furthermore, while pulmonary expression of tumor necrosis factor-α increased in sepsis, cytokine-induced neutrophil chemoattractant 2 increased in nephrectomized rats indicating that different inflammatory mediators were involved in the injury mechanism. Finally, pulmonary expression of multiple HSPs including HSP27-1, HSP70, HSP70-4, HSP70-8 and HSP90 was significantly different between the two conditions. Conclusions: We conclude that the pathophysiology of ARDS following ARF is distinct from that in sepsis. ARF-induced ARDS is characterized by a low level of cellular infiltration, induction of cytokine-induced neutrophil chemoattractant 2, and a discrete expression profile of HSPs.

The RIFLE Score Increases the Accuracy of Outcome Prediction in Patients with Acute Respiratory Distress Syndrome Undergoing Open Lung Biopsy

“…The relationship between pulmonary failure and mortality has been evaluated extensively in studies of ARDS patients; however, experimental results differ considerably [24,25,26,27,28]. Esteban et al [28] determined that independent prognostic factors were coma, ARDS and sepsis in patients on mechanical ventilation.…”

Selective Depletion of Alveolar Macrophages in Polymicrobial Sepsis Increases Lung Injury, Bacterial Load and Mortality but Does Not Affect Cytokine Release

“…Previous studies have suggested that AM may also play a role in the development of secondary pulmonary disorders like acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) [16, 17]. Common causes of indirect lung injury leading to ALI and ARDS are extrapulmonary foci such as peritonitis, pancreatitis, trauma, massive transfusions, or major surgery [18,19,20,21,22]. However, the question of whether AM are affected by extrapulmonary infections or rather actively participate in the development of sepsis, e.g.…”

Absence of Alveolar Tears in Rat Lungs with Significant Alveolar Instability

“…The intermittent peak airway pressure may still have been sufficient to cause an increase in alveolar epithelial permeability. In addition, ARDS caused by sepsis or acute renal failure [24] could make the lungs more susceptible to alveolar tearing compared with normal lungs subjected to injurious mechanical ventilation as in the study.…”